The invention relates to a new method of fabricating microfluidic devices, and also to the devices resulting from the application of this method, and their uses in microfluidic systems.
In numerous technical fields, microfluidics is being employed more and more often, whether in chemistry, in biotechnologies or in fluid mechanics, for example, with a demand on the part of users for even greater miniaturization.
In particular there is a demand for rapid prototyping techniques which allow the fabrication of microfluidic devices featuring greater complexity, shorter fabrication times, and lower costs. Furthermore, in accordance with the intended uses, the qualities of resistance to solvents (organic or aqueous), of resistance to the pressure exerted by the circulating fluid, of spatial resolution or of transparency constitute requirements which are conventional in the subject.
Conventionally there are two main approaches to the fabrication of microfluidic devices:                (i) direct etching and        (ii) replication by molding.        
In the direct etching techniques, the channels are etched directly by thin-layer structuring techniques from microelectronics (electron lithography, optical lithography, reactive ion etching, etc.). The devices are finished by assembly of thin layers (anodic bonding, fusion bonding, etc.). The materials employed are silicon, glass and metals.
This approach, however, is poorly adapted to rapid prototyping, since the equipment is expensive and its operation is complex and requires very specific know-how. The fabrication times are long and the choice of materials that can be used is limited.
In the molding or hot stamping techniques, an original mold is made by direct etching processes. The micro-fluidic devices are obtained by replication of the mold in a polymeric material. The use of PolyDiMethylSiloxane (PDMS) elastomers is by far the most widespread. This results in practice in a stamp of centimeter-scale thickness on its surface. The devices are finished by closing the structures by adhesive bonding to a flat surface (glass, elastomers, silicon, etc.).
So-called Soft Lithography techniques based on the use of elastomers greatly limit the capacity of the devices to withstand the application of high pressures (deformability and adhesive bonding) and therefore to withstand the transport of viscous fluids and the use of various solvents (organic or aqueous).
Devices made wholly of PDMS are unsatisfactory to users: the construction of micron-scale structures and/or of high aspect ratios is made impossible by the deformability of the channels, which can lead to the collapse and/or blocking of channels. This is the case with devices constructed from at least one element made of PDMS.
Ultimately, PDMS possesses poor chemical and mechanical resistance properties. PDMS is swollen by many organic solvents. It is broken down by strong bases and acids. These two characteristics greatly limit the range of solvents that can be transported in PDMS devices. The low elastic modulus of elastomers such as PDMS makes these materials completely ineffective at withstanding high mechanical pressures. Finally, PDMS is permeable to gases. The base and/or the cover of the PDMS devices are thick in order to allow them to be handled. This thickness interferes with observation of the interior of the channels by optical processes.
The use of other polymeric materials (vitreous materials in particular) is greatly limited by the step of closing of the channels by adhesive bonding. In practice, adhesive bonding on metallic and inorganic substrates remains an insurmountable barrier, especially for devices which include micron and submicron structures. The use of fine polymer layers to facilitate adhesive bonding is detrimental to the optical properties of the device, increases the overall thickness of the device, and alters its surface properties.
The present invention eliminates the drawbacks of the prior art by virtue of a new method of fabricating polymeric microfluidic devices by photo-assisted imprinting.
This fabrication process employs simple and inexpensive equipment and can be used in rapid prototyping. It provides access to devices which have a high spatial resolution, are transparent, resist organic and aqueous solvents, withstand pressures, are of reduced size, and are capable of integrating different materials.
Document WO 2005/030822 describes a method of fabricating a microfluidic device on the basis of photocrosslinkable perfluoropolyethers. A rigid substrate having a defined profile is used as a molding support. A liquid perfluoropolyether polymer precursor is placed on the mold. Photocrosslinking of the polymer gives a part of the device comprising the imprint of the molding. This part is removed from the mold and placed in contact with a support of the same material. A second irradiation attaches the two parts of the device.
This method is not without drawbacks: the perfluoro-polyether is selected for its qualities of elasticity, which allow it to be removed easily from the mold, and for its solvent resistance. However, the requirement to be able to displace the molded polymer means that it must be given a base with a sufficient thickness, which limits the use of this process for the following purposes: ensuring rapid thermal control, conserving the optical properties of the base, etc. The elastomeric material has by nature a poor resolution; it is difficult to obtain structures featuring channels with a size of less than 100 μm. Lastly, these devices are difficult to stack.
T. Cabral et al., Langmuir, Research Article, 2004, 20(23), 10020-10029, describe a method of fabricating microfluidic devices by frontal photopolymerization. A photocrosslinkable polymer is placed between two plates which are held apart by means of spacers, and a treatment with UV allows the polymer to be solidified in accordance with the selected profile. The use of spacers, however, restricts production to structures with a thickness of approximately 400 μm. The patterns that can be obtained by this method have a size which is greater than the optical wavelength employed. The channels obtained by this method have a width of 600 μm. The noncrosslinked polymer is removed by means of a solvent and by introducing pressurized air into the microcircuit. It is impossible, however, to remove all traces of prepolymer entirely, especially in the parts of the circuit that lack an outlet.
Finally, the need to irradiate the polymer through a glass strip imposes low resolution on the device, owing to the diffraction of luminous radiation through the glass strip. The supports which can be used by this method are few.
Document US 2006/0014271 describes a method of fabricating an entirely polymeric microfluidic device. However, the drawbacks are essentially the same as for the above method: thickness of the device and poor resolution.
V. Studer et al., Applied Physics Letters, 80(19), 3614-3616, 2002 describe a method of hot-nanomolding thermoplastic polymer pellets to form microfluidic devices. The resulting devices have satisfactory resolution and satisfactory solvent resistance, but their resistance to pressure is wanting, since the thermal bonding of the two polymeric parts does not allow the production of structures which are resistant to high pressures. Moreover, this process does not allow the finishing of the devices by adhesive bonding in an aqueous medium.
Jakeway et al., Proceedings of the International Conference on MEMS, Nano and smart systems, Jul. 20-23, 2003, pp. 118-122, and H. Lee et al., Microtechnology in Medicine and Biology, May 12, 2005, 237-240, describe a method of fabricating an article which comprises a base and side parts forming a channel. This article is produced by imprinting a stamp in a photo-crosslinkable resin and then carrying out UV irradiation. These articles, however, do not include a cover, and there is no known process allowing the closure of such a device under conditions permitting its use in microfluidics (imperviousness to liquids, resistance to pressure, resistance to solvents). The processes known to date for closing a nonthermoplastic microfluidic device require the use of a glue, or a surface treatment, which alter the chemical properties of the materials employed.
There is therefore still a need for a method that allows microfluidic devices to be produced by rapid prototyping, which is simple, inexpensive, and yields a product that features very high resolution, high resistance to aqueous or organic solvents and to pressure, with dimensions which can be reduced down to channels of micron size order.